title: The effects of tempol on renal function and hemodynamics in cyclosporine-induced renal insufficiency rats.
abstract: This study investigated the effects of tempol, a superoxide dismutase (SOD) mimetic and L-NAME, a nitric oxide (NO) synthase inhibitor on the renal function and hemodynamics in cyclosporine A (CsA) induced renal insufficiency rats. Male Sprague-Dawley rats were treated with either vehicle (C), tempol (T, 1 mmol/L in drinking fluid), L-NAME (L, 1 mmol/L in drinking fluid), CsA (Cs, 25 mg/kg/day via gavage), CsA plus tempol (TCs), CsA plus L-NAME (LCs) or CsA plus a combination of tempol and L-NAME (TLCs) for 21 consecutive days. At the end of treatment regimen, the renal responses to noradrenaline (NA), phenylephrine (PE), methoxamine and angiotensin II (Ang II) were determined. Cs and LCs rats had lower creatinine clearance (0.7 ± 0.1 and 0.6 ± 0.5 vs. 1.3 ± 0.2 mL/min/kg) and fractional excretion of sodium (0.12 ± 0.02 and 0.17 ± 0.01 vs. 0.67 ± 0.04%) but higher systolic blood pressure (145 ± 2 and 178 ± 4 vs. 116 ± 2) compared to the control (all p < 0.05), respectively. Tempol treatment in TCs or TLCs prevented the increase in blood pressure and improved creatinine clearance and sodium excretion compared to untreated Cs. The renal vasoconstriction in Cs or LCs to NA, PE and Ang II were lower than control by ∼35-48% (all p < 0.05). In TCs or TLCs, there was enhanced renal vasoconstriction to all agonist by ∼39-114% compared to Cs. SOD is important to counterbalance the hypertensive effect of a defective NO system and to allow the normal vasoconstrictor response of the renal vasculature to adrenergic agonists and Ang II in a model of CsA-induced renal insufficiency.
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
authors.forename: Tan Y
authors.initials: TY
authors.lastname: Chia
authors.forename: Munavvar A
authors.initials: MA
authors.lastname: Sattar
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Abdulla
authors.forename: Hassaan A
authors.initials: HA
authors.lastname: Rathore
authors.forename: Fiaz ud Din
authors.initials: Fu
authors.lastname: Ahmad
authors.forename: Gurjeet
authors.initials: G
authors.lastname: Kaur
authors.forename: Nor A
authors.initials: NA
authors.lastname: Abdullah
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Johns
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007668:Kidney / Q000098:blood supply; D007671:Kidney Concentrating Ability / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D051437:Renal Insufficiency / Q000139:chemically induced / Q000503:physiopathology; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D009569:Nitric Oxide; D016572:Cyclosporine; D013482:Superoxide Dismutase; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester